“类器官”，即三维自组织器官样微型组织，被提议作为中间模型，弥合药物开发中动物和人类研究之间的差距。尽管最近在类器官模型开发方面取得了进展，但使用这些模型进行的毒性研究仍然有限。因此，在本研究中，我们旨在分析源自诱导多能干细胞的分化前和分化后人肝类器官的功能和基因表达，并利用它们进行毒性评估。首先，我们通过各种功能评估，如糖原储存、白蛋白和胆汁酸分泌以及细胞色素 P450 (CYP) 活性，证实了该肝类器官模型与人类肝脏的功能相似性。随后，利用这些经过功能验证的肝类器官，我们对三种肝毒性物质（酮康唑、曲格列酮和托卡朋）和三种非肝毒性物质（蔗糖、抗坏血酸、和生物素）。这些类器官有效地区分了具有和不具有肝毒性的物质的毒性水平。通过分析肝毒性药物处理的类器官中发生的毒理学变化，我们证明了具有经过验证的功能和遗传特征的肝类器官作为毒性评估有前途的模型的潜力。

"Organoids", three-dimensional self-organized organ-like miniature tissues, are proposed as intermediary models that bridge the gap between animal and human studies in drug development. Despite recent advancements in organoid model development, studies on toxicity using these models are limited. Therefore, in this study, we aimed to analyze the functionality and gene expression of pre- and post-differentiated human hepatic organoids derived from induced pluripotent stem cells and utilize them for toxicity assessment. First, we confirmed the functional similarity of this hepatic organoid model to the human liver through various functional assessments, such as glycogen storage, albumin and bile acid secretion, and cytochrome P450 (CYP) activity. Subsequently, utilizing these functionally validated hepatic organoids, we conducted toxicity evaluations with three hepatotoxic substances (ketoconazole, troglitazone, and tolcapone), which are well known for causing drug-induced liver injury, and three non-hepatotoxic substances (sucrose, ascorbic acid, and biotin). The organoids effectively distinguished between the toxicity levels of substances with and without hepatic toxicity. We demonstrated the potential of hepatic organoids with validated functionalities and genetic characteristics as promising models for toxicity evaluation by analyzing toxicological changes occurring in hepatoxic drug-treated organoids.